A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters
Transcriptomics Dataset
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| Accession | GSE29282 |
| Title | A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters |
| Description | BCL6 is crucial for B-cell activation and lymphomagenesis. We used integrative genomics to explore BCL6 mechanism in normal and malignant B-cells. Surprisingly, BCL6 assembled distinct complexes at enhancers vs. promoters. At enhancers BCL6 preferentially recruited SMRT, which mediated H3K27 deacetylation through HDAC3, antagonized p300 activity and repressed transcription, but without decommissioning enhancers. This provides a biochemical basis for toggling enhancers from the active to poised state. Virtually all SMRT was bound with BCL6 suggesting that in B-cells BCL6 uniquely sequesters SMRT from other factors. In promoters BCL6 preferentially recruited BCOR, but most potently repressed promoters where it formed a distinctive ternary complex with SMRT and BCOR. Promoter repression was associated with decreased H3K36me3, H3K79me2 and Pol II elongation, linking BCL6 to transcriptional pausing. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29282 |
| Repository | Gene Expression Omnibus |
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